Bevacizumab Plus Capecitabine (Xeloda) in Patients With Untreated Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00203411
• Recruitment Status: Completed
• First Posted: September 20, 2005
• Results First Posted: February 6, 2017
• Last Update Posted: February 6, 2017
• Sponsor: Translational Oncology Research International
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Translational Oncology Research International

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer
• Interventions: Drug: Capecitabine (Xeloda); Drug: Bevacizumab
• Enrollment: 45

Participant Flow

Recruitment Details	Dates of recruitment period: October 2005 to February 2009 Types of location: Academic medical oncology clinical and community medical oncology clinics
Pre-assignment Details

Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description	Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent. Capecitabine (Xeloda): 1000mg/m2 administered orally twice daily for two weeks followed by one week rest period Bevacizumab: 7.5 mg/kg IV will be administered every 3 weeks
Period Title: Treatment Period
Started	45
Completed	45
Not Completed	0
Period Title: Follow-up
Started	45
Completed	41
Not Completed	4
Reason Not Completed
Progressive Disease	4

Baseline Characteristics

Arm/Group Title		Bevacizumab Plus Capecitabine
Arm/Group Description		Bevacizumab 7.5 mg/kg every 3 weeks will be administered interavenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Overall Number of Baseline Participants		45
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	45 participants
		79; (54 to 93)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Female	27 60.0%
	Male	18 40.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 8.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	3 6.7%
	White	36 80.0%
	More than one race	0 0.0%
	Unknown or Not Reported	2 4.4%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	45 participants
		45
Eastern Cooperative Oncology Group (ECOG) [1]; Measure Type: Number; Unit of measure: Subjects	Number Analyzed	45 participants
Score of 1		17
Score of 2		28
		[1] Measure Description: ECOG Grade Evaluated by Physical Exam 0 Fully active, able to carry on all predisease activities with restriction; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Ambulatory and capable of all self-care but unable to carry out any work activities. Out of bed > 50%; Capable of only limited self-care, confined to bed or chair > 50% waking hours; Completely disabled, cannot carry on any self-care, totally confined to bed or chair

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression
Description	Progression Free Survival (PFS)- the interval from the date of enrollment to the first documented date of disease progression, death due to cancer, or the last date of a definitive assessment (not an unknown assessment) at which the patient is known to be progression-free. If there is an unknown assessment, then (a) if the next subsequent definitive assessment is complete response (CR), partial response (PR), or stable disease (SD), the patient is considered to be progression-free at the date of the subsequent definitive assessment and PFS is calculated as above; (b) if the next subsequent definitive assessment is progressive disease (PD), the patient is considered to be a failure at the time of the (earliest) assessment of unknown preceding the documented disease progression (i.e. PFS is back-dated to the date of the unknown assessment) and (c) if there is no subsequent definitive assessment, PFS for the patient is considered to be a censored observation at the date
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Overall Number of Participants Analyzed	45
Median (95% Confidence Interval); Unit of Measure: months
	6.87; (5.1 to 11.5)

2. Primary Outcome

Title	Number of Subjects Requiring Dose Modifications
Description	Number of Subjects that required Bevacizumab or Capecitabine dose modifications, delay, reduction or discontinuation due to adverse reactions.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

all subjects that received chemotherapy

Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Overall Number of Participants Analyzed	45
Measure Type: Number; Unit of Measure: participants
Delay in Bevacizumab Dose	15
Discontinuation of Bevacizumab	14
Delay in Capec itabineDose	8
Reduction of Capecitabine Dose	13
Discontinuation of Capecitabine	16

3. Secondary Outcome

Title	Response Rates
Description	Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time Frame	every 21 days up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Overall Number of Participants Analyzed	45
Measure Type: Number; Unit of Measure: participants
Complete Response	2
Partial Response	14
Stable Disease	16
Progression	9
Not Evaluable	4

4. Secondary Outcome

Title	Quality of Life of Patients
Description	Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Trial Outcome Index (TOI) – a questionnaire assessing quality of life concerns pertinent to colorectal cancer patients. Questions address Physical, Emotional and Functional Well-Being. Scale: Not at all (0), A little bit (1), Somewhat (2), Quite a bit (3), and very much (4). Higher numbers indicate a better state of well being. Scale 0 -136. Higher numbers indicating a better state of well-being. The Overall scores for the FACT-C Composite scale range between 0-100 with higher scores indicating a better state of well being. The EQ VAS= Euro Quality of Life 5 Dimension Self Reported Healthstate. It records the respondent’s self-rated health on a vertical, visual analogue scale where the endpoints are labeled 0 ‘Best imaginable health state’ and 100 ‘Worst imaginable health state’.
Time Frame	Baseline, Cycle 2, and End of Study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
Overall Number of Participants Analyzed	45
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline FACT-C Trial outcome index (TOI)	62.85 (12.12)
Cycle 2 FACT-C TOI	66.31 (10.32)
End of Study FACT-C TOI	62.09 (12.12)
Baseline FACT-C Composite	99.87 (19.87)
Cycle 2 FACT-C Composite	105.38 (17.02)
End of Study FACT-Composite	98.61 (21.73)
Baseline EQ-5D VAS	61.76 (23.17)
Cycle 2 EQ-5D VAS	68.59 (22.26)
End of Study EQ-5D VAS	66.54 (23.18)

Adverse Events

Time Frame	From time of consent evaluated every 21 days until 30 days after last treatment, up to 1 year.
Adverse Event Reporting Description	Systemic adverse event assessment occurred every through investigator assessment during the Treatment period
Arm/Group Title	Bevacizumab Plus Capecitabine
Arm/Group Description	Bevacizumab 7.5 mg/kg every 3 weeks will be administered intravenously (IV) to the enrolled patients. Oral capecitabine 1000 mg/m^2 twice daily for 14 days followed by 7 days off every 21 days. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of patient consent.
All-Cause Mortality
	Bevacizumab Plus Capecitabine
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Bevacizumab Plus Capecitabine
	Affected / at Risk (%)	# Events
Total	45/45 (100.00%)
Blood and lymphatic system disorders
Leukopenia † 1	1/45 (2.22%)	1
Dyspepsia † 1	1/45 (2.22%)	1
Gastrointestinal disorders
Diarrhea † 1	8/45 (17.78%)	8
Dehydration † 1	4/45 (8.89%)	4
Vomiting † 1	3/45 (6.67%)	3
Nausea † 1	2/45 (4.44%)	2
Mucositis † 1	2/45 (4.44%)	2
Anorexia † 1	2/45 (4.44%)	2
Bloating † 1	2/45 (4.44%)	2
Hemorrhage-GI † 1	1/45 (2.22%)	1
Obstruction † 1	2/45 (4.44%)	2
Infarction † 1	1/45 (2.22%)	1
General disorders
Fatigue † 1	6/45 (13.33%)	6
Pain-Abdomen † 1	2/45 (4.44%)	2
Hepatobiliary disorders
Liver Failure † 1	1/45 (2.22%)	1
Renal Failure † 1	1/45 (2.22%)	1
Nervous system disorders
Cerebral vascular accident † 1	1/45 (2.22%)	1
Skin and subcutaneous tissue disorders
Hand Foot Skin Reaction † 1	6/45 (13.33%)	6
Vascular disorders
Hypertension † 1	3/45 (6.67%)	3
Deep vein thrombosis † 1	1/45 (2.22%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (Unspecified)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bevacizumab Plus Capecitabine
	Affected / at Risk (%)	# Events
Total	30/45 (66.67%)
Blood and lymphatic system disorders
Anemia † 2	13/45 (28.89%)	13
Thrombocytopenia † 2	8/45 (17.78%)	8
Leukopenia † 2	7/45 (15.56%)	7
Hemorrhage-Nose † 2	6/45 (13.33%)	6
Edema-limb † 2	5/45 (11.11%)	5
Ear and labyrinth disorders
Dizziness † 2	5/45 (11.11%)	5
Gastrointestinal disorders
Diarrhea † 1	28/45 (62.22%)	28
Nausea † 1	21/45 (46.67%)	21
Mucositis † 2	16/45 (35.56%)	16
Anorexia † 2	15/45 (33.33%)	15
Vomiting † 2	9/45 (20.00%)	9
Dehydration † 2	7/45 (15.56%)	7
General disorders
Fatigue † 1	30/45 (66.67%)	30
Memory Impairment † 2	5/45 (11.11%)	5
Metabolism and nutrition disorders
Weight Loss † 2	5/45 (11.11%)	5
Nervous system disorders
Neuropathy † 2	11/45 (24.44%)	11
Pain-Abdomen † 2	10/45 (22.22%)	10
Pain-Head † 2	5/45 (11.11%)	5
Renal and urinary disorders
Proteinuria † 2	7/45 (15.56%)	7
Skin and subcutaneous tissue disorders
Hand Foot Skin Reaction † 2	24/45 (53.33%)	24
Dry Skin † 2	8/45 (17.78%)	8
Rash † 2	7/45 (15.56%)	7
Vascular disorders
Hypertension † 2	10/45 (22.22%)	10
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, Criteria for Adverse; 2 Term from vocabulary, CTCAE (Unspecified)

Limitations and Caveats

This was a small study with only 45 participants who received study treatment. With such a small sample size the study does not have the statistical power to make categorical assessments or statements.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Arash Naeim
• Organization: Translational Research in Oncology
• Phone: 310 267-6810
• EMail: anaeim@mednet.ucla.edu

• Responsible Party: Translational Oncology Research International
• ClinicalTrials.gov Identifier: NCT00203411 History of Changes
• Obsolete Identifiers: NCT00217685
• Other Study ID Numbers: TORI GI-04
• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Results First Submitted: February 10, 2016
• Results First Posted: February 6, 2017
• Last Update Posted: February 6, 2017